Journal article

Protein disulphide isomerase protects against protein aggregation and is S-nitrosylated in amyotrophic lateral sclerosis

Adam K Walker, Manal A Farg, Chris R Bye, Catriona A McLean, Malcolm K Horne, Julie D Atkin

BRAIN | OXFORD UNIV PRESS | Published : 2010


Amyotrophic lateral sclerosis is a rapidly progressing fatal neurodegenerative disease characterized by the presence of protein inclusions within affected motor neurons. Endoplasmic reticulum stress leading to apoptosis was recently recognized to be an important process in the pathogenesis of sporadic human amyotrophic lateral sclerosis as well as in transgenic models of mutant superoxide dismutase 1-linked familial amyotrophic lateral sclerosis. Endoplasmic reticulum stress occurs early in disease, indicating a critical role in pathogenesis, and involves upregulation of an important endoplasmic reticulum chaperone, protein disulphide isomerase. We aimed to investigate the involvement of pro..

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Funding Acknowledgements

We thank Professor Neil Bulleid, University of Manchester, for the pCMV5 vector encoding human PDI, and Professor Neil Cashman, University of Toronto, for the NSC-34 cell line. We also thank Dr Bradley Turner for helpful input on the manuscript, and Kai Ying Soo and Professor Philip Nagley for technical assistance and access to unpublished data. Human spinal cord tissues were received from the MND Research Tissue Bank of Victoria, supported by the Victorian Brain Bank Network, the Mental Health Research Institute, Alfred Hospital, Victorian Forensic Institute of Medicine, The University of Melbourne, and funded by MND Research Institute of Australia and the Bethlehem Griffiths Research Foundation.